Triethylamine → 7-{6-[(3,3-Dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}-5,7-diazaspiro[3.4]octane-6,8-dione

HRID 527692노트

반응식

HRID 527692 반응식
[NH2:1][C:2]1([C:6]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][C:16]3[C:21]4[C:22]([CH3:26])([CH3:25])[CH2:23][O:24][C:20]=4[CH:19]=[CH:18][CH:17]=3)=[CH:13][CH:14]=2)=[O:7])[CH2:5][CH2:4][CH2:3]1.C(N(CC)CC)C.Cl[C:35](Cl)([O:37]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:25][C:22]1([CH3:26])[C:21]2[C:16]([O:15][C:12]3[N:11]=[CH:10][C:9]([N:8]4[C:6](=[O:7])[C:2]5([CH2:5][CH2:4][CH2:3]5)[NH:1][C:35]4=[O:37])=[CH:14][CH:13]=3)=[CH:17][CH:18]=[CH:19][C:20]=2[O:24][CH2:23]1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 94429Triphosgene2회HCID 679668331-amino-N-{6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}cyclobutanecarboxamide2회

생성물 1

HCID 574102217-{6-[(3,3-Dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}-5,7-diazaspiro[3.4]octane-6,8-dione

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

반응 조건

온도
0 °C

실험 절차

1-amino-N-{6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}cyclobutanecarboxamide (Intermediate 70, 17 mg) was dissolved in dry dichloromethane (1.8 ml). The reaction mixture was cooled down in an ice bath. Triethylamine (39.48 μl, 0.283 mmol) was added at 0° C. Then 0.89 ml of a solution of triphosgene in dry dichloromethane was added dropwise (0.0135 mg, 4.00 mg). The reaction mixture was stirred under argon during 10 min at 0° C., then during 30 min at room temperature. Then an additional 0.25 equivalent of triphosgene in dichloromethane (0.26 M solution) was added at 0° C. and the reaction mixture was stirred under argon an additional 30 min at room temperature. The solvents were removed under vacuum. The residue obtained was purified by flash chromatography on silica gel (Companion system, 4 g silica cartridge) with cyclohexane/ethylacetate as eluents from 100/0 to 55/45. This afforded the title compound (12 mg).

후처리

  1. temperatureThe reaction mixture was cooled down in an ice bath
  2. waitduring 30 min at room temperature
  3. stirringthe reaction mixture was stirred under argon an additional 30 min at room temperature
  4. customThe solvents were removed under vacuum
  5. customThe residue obtained
  6. customwas purified by flash chromatography on silica gel (Companion system, 4 g silica cartridge) with cyclohexane/ethylacetate as eluents from 100/0 to 55/45

출처 및 근거

ORD 기록
ord-8236b984068a4aa2995d3af2fe160e2e
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346790B2

반응 노트

불러오는 중…